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European Journal of Pediatrics

, Volume 177, Issue 6, pp 827–834 | Cite as

Weekly regimen of vitamin D supplementation is more efficacious than stoss regimen for treatment of vitamin D deficiency in children with chronic liver diseases

  • Bikrant Bihari Lal
  • Seema Alam
  • Rajeev Khanna
  • Dinesh Rawat
Original Article

Abstract

There are no evidence-based recommendations on the ideal dose and regimen for supplementation of vitamin D in children with chronic liver disease (CLD). This study aimed to compare the safety and efficacy of weekly and stoss regimens for treatment of vitamin D deficiency in these children. Children between the ages of 1 to 18 years with CLD and hypovitaminosis D defined by 25-OH vitamin D (25(OH)D) < 30µg/l were included. They were randomized to receive either stoss regimen (600,000 IU on day 1) or weekly (60,000 IU weekly) regimen of vitamin D. The 25(OH)D levels at 3 and 6 months were compared in the two groups. A total of 210 suspected cases of CLD were assessed for eligibility. Of a total of 67 children satisfying the inclusion criteria, 33 and 34 were randomized to receive stoss and weekly regimen, respectively. Final analysis included 28 children in each group. Clinical rickets was seen in 25.4% of children with hypovitaminosis D. The rise in levels of 25(OH)D at 3 months was higher with weekly regimen (34.3 ± 30.7 µg/l) as compared to stoss regimen (17.2 ± 11.5 µg/l) (p = 0.009). Rise at 6 months as compared to baseline was significantly higher with weekly regimen (30.7 ± 24µg/l) as compared to stoss regimen (11 ± 8.4 µg/l) (p < 0.001). Normal levels of 25(OH)D at 6 months were achieved in 24/28 (85.7%) of those receiving weekly regimen and 9/28 (32.1%) of those receiving stoss regimen (p < 0.001). With stoss therapy, 25(OH)D increased at 3 months as compared to baseline but thereafter dropped significantly at 6 months (p = 0.008).

Conclusion: Weekly regimen of vitamin D supplementation is more effective than stoss regimen for treatment of hypovitaminosis D in children with CLD. Once normal levels are achieved, child should be shifted to 60,000 IU per month as maintenance dose.

What is Known:

Vitamin D deficiency is more common and severe in children with chronic liver diseases.

Currently used doses fail to achieve normal vitamin D levels in these children.

What is New?

Weekly regimen of 60,000 IU of vitamin D3 is the most effective regimen for treating vitamin D deficiency in children with CLD.

Children with CLD should further receive maintenance dose of 60,000 IU every month.

Keywords

Chronic liver disease Stoss regimen Vitamin D deficiency 

Abbreviations

APRI

AST to platelet ratio index

BMP

Bone morphogenetic protein

CLD

Chronic liver disease

MMP

Matrix metalloproteinases

PELD

Pediatric end-stage liver disease

PTH

Parathormone

RDA

Recommended daily allowance

VDBP

Vitamin D binding protein

VDD

Vitamin D deficiency

Notes

Authors’ Contributions

BBL and SA conceptualized and designed the work. BBL collected the data. SA and BBL analysed the data and prepared the first draft. SA, BBL, DR and RK critically reviewed, revised and approved the final version.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical approval Number: IEC/IRB-F.25/5/75/ILBS/AC/2014/387.

Informed consent

Informed consent was obtained from the parents of all the children included in the study.

Supplementary material

431_2018_3123_MOESM1_ESM.docx (12 kb)
ESM 1 (DOCX 11.6 kb)

References

  1. 1.
    Abramovitch S, Dahan-Bachar L, Sharvit E, Weisman Y, Tov AB, Brazowski E, Reif S (2011) Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut 60:1728–1737CrossRefPubMedGoogle Scholar
  2. 2.
    Angurana SK, Angurana RS, Mahajan G, Kumar N, Mahajan V (2014) Prevalence of vitamin D deficiency in apparently healthy children in north India. J Pediatr Endocrinol Metab 27:1151–1156PubMedGoogle Scholar
  3. 3.
    Artaza JN, Norris JC (2009) Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol 200:207–221CrossRefPubMedGoogle Scholar
  4. 4.
    Arteh J, Narrah S, Nair S (2010) Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci 55:2624–2628CrossRefPubMedGoogle Scholar
  5. 5.
    Balasubramanian S, Dhanalakshmi K, Amperayani S (2013) Vitamin D deficiency in childhood—a review on current guidelines on diagnosis and management. Indian Pediatr 50:669–675CrossRefPubMedGoogle Scholar
  6. 6.
    Cesur Y, Caksen H, Gundem A, Kirimi E, Odabas D (2003) Comparison of low and high dose of vitamin D treatment in nutritional vitamin D deficiency rickets. J Pediatr Endocrinol Metab 16:1105–1109CrossRefPubMedGoogle Scholar
  7. 7.
    Cioffi M, Corradino M, Gazzero P, Vietri MT, Di Macchia C, Contursi A, Colicigno R, Catalano T, Molinari AM (2000) Serum concentrations of intact parathyroid hormone in healthy children. Clin Chem 6:863–864Google Scholar
  8. 8.
    Emel T, Dokan DA, Erdem G, Faruk O (2012) Therapy strategies in vitamin D deficiency with or without rickets: efficiency of low-dose stoss therapy. J Pediatr Endocrinol Metab 25:107–110CrossRefPubMedGoogle Scholar
  9. 9.
    Fisher L, Fisher A (2007) Vitamin D and parathyroid hormone in outpatients with non-cholestatic chronic liver disease. Clin Gastroenterol Hepatol 5:513–520CrossRefPubMedGoogle Scholar
  10. 10.
    Gordon CM, Williams A, Feldman HA, May J, Sinclair L, Vasquez A, Cox JE (2008) Treatment of hypovitaminosis D in infants and toddlers. J Clin Endocrinol Metab 93:2716–2721CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281CrossRefPubMedGoogle Scholar
  12. 12.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930CrossRefPubMedGoogle Scholar
  13. 13.
    Kitson MT, Roberts SK (2012) D-livering the message: the importance of vitamin D status in chronic liver disease. J Hepatol 57:897–909CrossRefPubMedGoogle Scholar
  14. 14.
    Markestad T, Hesse V, Siebenhuner M, Jahreis G, Aksnes L, Plenert W, Aarskog D (1987) Intermittent high-dose vitamin D prophylaxis during infancy: effect on vitamin D metabolites, calcium, and phosphorus. Am J Clin Nutr 46:562–568CrossRefGoogle Scholar
  15. 15.
    Metz MP (2006) Determining urinary calcium/creatinine cutoffs for the paediatric population using published data (2006). Ann Clin Biochem 43:398–401CrossRefPubMedGoogle Scholar
  16. 16.
    Molgaard C, Michaelsen KF (2003) Vitamin D and bone health in early life. Proc Nutr Soc 62(4):823–828CrossRefPubMedGoogle Scholar
  17. 17.
    Mondal K, Seth A, Marwaha RK, Dhanwal D, Aneja S, Singh R, Sonkar P (2014) A randomized controlled trial on safety and efficacy of single intramuscular versus staggered oral dose of 600 000IU vitamin D in treatment of nutritional rickets. J Trop Pediatr 60(3):203–210CrossRefPubMedGoogle Scholar
  18. 18.
    Pappa H, Mitchell PD, Jiang H, Kassiff S, Philip-Dhima R, DiFabio D, Quinn N, Lawton RC, Varvaris M, Van Straaten S, Gordon CM (2012) Treatment of vitamin D insufficiency in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing three regimens. J Clin Endocrinol Metab 97:2134–2142CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ramirez AM, Wongtrakool C, Welch T, Steinmeyer A, Zügel U, Roman J (2010) Vitamin D inhibition of pro-fibrotic effects of transforming growth factor beta1 in lung fibroblasts and epithelial cells. J Steroid Biochem Mol Biol 118:142–150CrossRefPubMedGoogle Scholar
  20. 20.
    Shepherd D, Belessis Y, Katz T, Morton J, Field P, Jaffe A (2013) Single high-dose oral vitamin D3 (stoss) therapy—a solution to vitamin D deficiency in children with cystic fibrosis? J Cystic Fibrosis 12:177–182CrossRefGoogle Scholar
  21. 21.
    Shneider BL, Magee JC, Bezzera JA, Haber B, Karpen SJ, Raghunathan T, Rosenthal P, Schwarz K, Suchy FJ, Kerkar N et al (2012) Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia. Pediatrics 130:607–614CrossRefGoogle Scholar
  22. 22.
    Stokes CS, Volmer DA, Grunhage F, Lammert F (2013) Vitamin D in chronic liver disease. Liver Int 33:338–352CrossRefPubMedGoogle Scholar
  23. 23.
    Vanstone MB, Oberfield S, Shader L, Ardeshirpour L, Carpenter TO (2012) Hypercalcemia in children receiving pharmacologic doses of vitamin D. Pediatrics 129:e1060–e1063CrossRefPubMedGoogle Scholar
  24. 24.
    Vieth R (1999) Vitamin D supplementation, 25-OH vitamin D concentrations and safety. Am J Clin Nutr 69:842–856CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Bikrant Bihari Lal
    • 1
  • Seema Alam
    • 1
  • Rajeev Khanna
    • 1
  • Dinesh Rawat
    • 1
  1. 1.Department of Pediatric HepatologyInstitute of Liver and Biliary SciencesNew DelhiIndia

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